(1/860) Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation.

1. The aim of the present study was to analyse the cardiovascular actions of the synthetic CB1/CB2 cannabinoid receptor agonist WIN55212-2, and specifically to determine its sites of action on sympathetic cardiovascular regulation. 2. Pithed rabbits in which the sympathetic outflow was continuously stimulated electrically or which received a pressor infusion of noradrenaline were used to study peripheral prejunctional and direct vascular effects, respectively. For studying effects on brain stem cardiovascular regulatory centres, drugs were administered into the cisterna cerebellomedullaris in conscious rabbits. Overall cardiovascular effects of the cannabinoid were studied in conscious rabbits with intravenous drug administration. 3. In pithed rabbits in which the sympathetic outflow was continuously electrically stimulated, intravenous injection of WIN55212-2 (5, 50 and 500 microg kg(-1)) markedly reduced blood pressure, the spillover of noradrenaline into plasma and the plasma noradrenaline concentration, and these effects were antagonized by the CB1 cannabinoid receptor-selective antagonist SR141716A. The hypotensive and the sympathoinhibitory effect of WIN55212-2 was shared by CP55940, another mixed CB1/CB2 cannabinoid receptor agonist, but not by WIN55212-3, the enantiomer of WIN55212-2, which lacks affinity for cannabinoid binding sites. WIN55212-2 had no effect on vascular tone established by infusion of noradrenaline in pithed rabbits. 4. Intracisternal application of WIN55212-2 (0.1, 1 and 10 microg kg(-1)) in conscious rabbits increased blood pressure and the plasma noradrenaline concentration and elicited bradycardia; this latter effect was antagonized by atropine. 5. In conscious animals, intravenous injection of WIN55212-2 (5 and 50 microg kg(-1)) caused bradycardia, slight hypotension, no change in the plasma noradrenaline concentration, and an increase in renal sympathetic nerve firing. The highest dose of WIN55212-2 (500 microg kg(-1)) elicited hypotension and tachycardia, and sympathetic nerve activity and the plasma noradrenaline concentration declined. 6. The results obtained in pithed rabbits indicate that activation of CB1 cannabinoid receptors leads to marked peripheral prejunctional inhibition of noradrenaline release from postganglionic sympathetic axons. Intracisternal application of WIN55212-2 uncovered two effects on brain stem cardiovascular centres: sympathoexcitation and activation of cardiac vagal fibres. The highest dose of systemically administered WIN55212-2 produced central sympathoinhibition; the primary site of this action is not known.  (+info)

(2/860) Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats.

It is known that arterial baroreflexes are suppressed in stressful conditions. The present study was designed to determine whether and how hypoxia affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia. In chloralose-urethane-anaesthetized rats, baroreflex vagal bradycardia was evoked by electrical stimulation of the aortic depressor nerve, and the effect of 15 s inhalation of hypoxic gas (4% O2) was studied. Inhalation of hypoxic gas was found to inhibit baroreflex vagal bradycardia. The inhibition persisted after bilateral transection of the carotid sinus nerve. Cervical vagus nerves were cut bilaterally and their peripheral cut ends were stimulated to provoke vagal bradycardia of peripheral origin so as to determine whether hypoxia could inhibit vagal bradycardia by acting on a peripheral site. In contrast to baroreflex vagal bradycardia, the vagus-induced bradycardia was not affected by hypoxic gas inhalation. It is concluded that baroreflex vagal bradycardia is inhibited by hypoxia and the inhibition is largely mediated by its direct central action.  (+info)

(3/860) Pseudo second degree atrioventricular block with bradycardia. Successful treatment with quinidine.

Pseudo second degree atrioventricular block resulting from blocked His premature beats was successfully treated with quinidine. The diagnosis was proved by His bundle electrogam which showed both blocked and conducted His premature beats. The blocked His prematures produced second degree atrioventricular block by making the atrioventricular junction refractory. Quinidine abolished both conducted and blocked His extrasystoles. There has been no recurrence of arrhythmia during a one-year follow-up.  (+info)

(4/860) Incidence of bradycardia during recovery from spinal anaesthesia: influence of patient position.

We administered 0.5% plain bupivacaine 4 ml intrathecally (L2-3 or L3-4) in three groups of 20 patients, according to the position in which they were nursed in the post-anaesthesia care unit (PACU): supine horizontal, 30 degrees Trendelenburg or hammock position (trunk and legs 30 degrees elevated). Patients were observed until anaesthesia descended to less than S1. The incidence of severe bradycardia (heart rate < 50 beat min-1) in the PACU was significantly higher in patients in the Trendelenburg position (60%) than in the horizontal (20%, P < 0.01) or hammock (10%, P < 0.005) position. After 90 min, following admission to the PACU, only patients in the hammock position did not have severe bradycardia. In this late phase, the incidence of severe bradycardia in the Trendelenburg group was 35% (P < 0.005) and 10% in patients in the supine horizontal position. In four patients, severe bradycardia first occurred later than 90 min after admission to the PACU. The latest occurrence of severe bradycardia was recorded 320 min after admission to the PACU. We conclude that for recovery from spinal anaesthesia, the Trendelenburg position should not be used and the hammock position is preferred.  (+info)

(5/860) Relation between mode of pacing and long-term survival in the very elderly.

OBJECTIVES: This study analyzes the relationship between pacing mode and long-term survival in a large group of very elderly patients (> or = 80 years old). BACKGROUND: The relationship between pacing mode and long-term survival is not clear. Because the number of very elderly who are candidates for pacing is increasing, issues related to pacemaker (PM) use in the elderly have important clinical and economic implications. METHODS: We retrospectively reviewed 432 patients (mean age, 84.5+/-3.9 years) who received their initial PM (ventricular in 310 and dual chamber in 122) between 1980 and 1992. Follow-up was complete (3.5+/-2.6 years). Observed survival was estimated by the Kaplan-Meier method. Age- and gender-matched cohorts from the Minnesota population were used for expected survival. Log-rank test and Cox regression hazard model were used for univariate and multivariate analyses. RESULTS: Patients with ventricular PMs appeared to have poor overall survival compared with those with dual-chamber PMs. Observed survival after PM implantation in high grade atrioventricular block (AVB) patients was significantly worse than expected survival of the age- and gender-matched population (p < 0.0001), whereas observed survival of patients with sinus node dysfunction was not significantly different from expected survival of the matched population (p = 0.413). By univariate analysis, ventricular pacing in patients with AVB appeared to be associated with poor survival compared with dual-chamber pacing (hazard ratio [HR] 2.08; 95% confidence interval [CI] 1.33 to 3.33). After multivariate analysis, this difference was no longer significant (HR 1.41; 95% CI 0.88 to 2.27). Independent predictors of all-cause mortality were number of comorbid illnesses, New York Heart Association functional class, left ventricular depression and older age at implant. Pacing mode was not an independent predictor of overall survival. Older age at implantation, diabetes mellitus, dementia, history of paroxysmal atrial fibrillation and earlier year of implantation were independent predictors of ventricular pacemaker selection. CONCLUSIONS: After PM implantation, long-term survival among very elderly patients was not affected by pacing mode after correction of baseline differences. Selection bias was present in pacing mode in the very elderly, with ventricular pacing selected for sicker and older patients, perhaps partly explaining the apparent "beneficial impact on survival" observed with dual-chamber pacing.  (+info)

(6/860) Relative bradycardia is not a feature of enteric fever in children.

We investigated pulse-temperature relationships in 66 children with enteric fever (group 1) and in 76 with other infections (group 2). Group 1 children were older than group 2 children (mean age +/- SD, 91 +/- 36 vs. 66 +/- 32 months, respectively; P < .001) and had mean oral temperatures +/- SD similar to those of group 2 children (38.3 +/- 1.0 vs. 38.3 +/- 0.9 degrees C, respectively; P > .2); however, group 1 children had lower mean baseline pulse rates +/- SD than did group 2 children (119 +/- 25 vs. 127 +/- 28 beats/min, respectively; P < .001). In a multiple linear regression model, pulse rate was independently associated with age (inversely; P < .001) and oral temperature (positively; P < .006) but not with diagnostic group or gender (P > .5). After adjustment of the mean initial pulse rate +/- SD to age of 72 months, there was no difference between group 1 and group 2 children (126 +/- 24 vs. 126 +/- 20 beats/min, respectively; P > .5). From 4 to 72 hours after commencement of treatment, the mean oral temperature in group 1 patients was approximately 0.3 degrees C higher than that in group 2 patients, and the age-adjusted pulse rate was 5 beats/min higher in group 1 children than in group 2 children. These data suggest that relative bradycardia is not characteristic of enteric fever in children.  (+info)

(7/860) Estrogen enhancement of baroreflex sensitivity is centrally mediated.

We have recently shown that estrogen enhances baroreceptor control of reflex bradycardia in conscious rats. The present study replicated this finding in pentobarbital sodium-anesthetized rats, and the study was extended to investigate whether this effect of estrogen is centrally or peripherally mediated. Hemodynamic responses to electrical stimulation of the central end of the aortic depressor or the vagal efferent nerve were evaluated in pentobarbital sodium-anesthetized sham-operated (SO), ovariectomized (OVX), and OVX estradiol-treated Sprague-Dawley rats. Phenylephrine (1-16 microgram/kg iv) elicited dose-dependent pressor and bradycardic responses. Regression analysis of the baroreflex curves, relating changes in mean arterial pressure and heart rate, revealed a significantly smaller baroreflex sensitivity in OVX compared with SO anesthetized rats (-0.54 +/- 0.05 and -0.91 +/- 0.12 beats. min-1. mmHg-1, respectively; P < 0.05). Treatment of OVX rats with 17beta-estradiol (E2, 50 microgram. kg-1. day-1 for 2 days subcutaneously) significantly enhanced baroreflex sensitivity to a level similar to that of SO rats (P < 0.05). The enhancing effect of E2 on the baroreflex-mediated bradycardia, observed in conscious and anesthetized rats, seems to be selective because the baroreflex-mediated tachycardic responses measured in a separate group of conscious rats were not altered by ovariectomy or E2 administration. Electrical stimulation of the aortic nerve elicited frequency-dependent depressor and bradycardic responses that were significantly smaller in OVX compared with SO values (P < 0.05). Treatment of OVX rats with E2 restored the hemodynamic responses to aortic stimulation to near SO levels. On the other hand, hemodynamic responses to vagal stimulation were not affected by OVX or treatment with E2. These findings suggest that enhancement of reflex bradycardia by estrogen is centrally mediated and involves interaction with central projections of the aortic nerve.  (+info)

(8/860) Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block.

BACKGROUND: It is a widely held view that congenital heart block (CHB) is caused by the transplacental transfer of maternal autoantibodies (anti-SSA/Ro and/or anti-SSB/La) into the fetal circulation. To test this hypothesis and to reproduce human CHB, an experimental mouse model (BALB/c) was developed by passive transfer of human autoantibodies into pregnant mice. METHODS AND RESULTS: Timed pregnant mice (n=54) were injected with a single intravenous bolus of purified IgG containing human anti-SSA/Ro and anti-SSB/La antibodies from mothers of children with CHB. To parallel the "window period" of susceptibility to CHB in humans, 3 groups of mice were used: 8, 11, and 16 days of gestation. Within each group, we tested 10, 25, 50, and 100 microg of IgG. At delivery, ECGs were recorded and analyzed for conduction abnormalities. Bradycardia and PR interval were significantly increased in 8-, 11-, and 16-day gestational groups when compared with controls (P<0.05). QRS duration was not significantly different between all groups. Antibody levels measured by ELISA in both mothers and their offspring confirmed the transplacental transfer of the human antibodies to the pups. CONCLUSIONS: The passive transfer model demonstrated bradycardia, first-degree but not complete atrioventricular block in pups. The greater percentage and degree of bradycardia and PR prolongation in the 11-day mouse group correlates with the "window period" of susceptibility observed in humans. The high incidence of bradycardia suggests possible sinoatrial node involvement. All together, these data provide relevant insights into the pathogenesis of CHB.  (+info)